Antiretroviral drugs not only help people living with HIV maintain good health and reduce the risk of transmission, but they can also prevent HIV-negative people from acquiring the virus. Pre-exposure prophylaxis—better known as PrEP—refers to pills or injections taken regularly to prevent HIV.

PrEP Options 

There are currently four antiretroviral options approved by the Food and Drug Administration (FDA) for HIV prevention:

  • Tenofovir disoproxil fumarate/emtricitabine, or TDF/FTC pills (Truvada or generic equivalents)
  • Tenofovir alafenamide/emtricitabine, or TAF/FTC pills (Descovy)
  • Long-acting cabotegravir injections (Apretude)
  • Long-acting lenacapavir injections (Yeztugo)

Click here for the POZ HIV Prevention Drug Chart for more information about each of the available options.

Truvada was approved for HIV prevention in 2012. It is indicated for all adults and adolescents at risk for sexually acquired HIV. It is usually taken once daily, but taking it “on demand” before and after sex—known as PrEP 2-1-1—also works well.

Studies of cisgender gay and bisexual men and transgender women found that daily it is around 99% effective if used consistently. TDF/FTC PrEP is also effective for cisgender women, though they may need to maintain better adherence for optimal protection.

TDF/FTC is generally safe and well tolerated, though it can cause minor side effects such nausea, which usually resolve after the first few weeks or months. TDF can cause impaired kidney function and bone loss in susceptible people, and it is not recommended for those with preexisting kidney problems. The drugs are also active against hepatitis B virus (HBV), and liver flare-ups can occur if people with HIV/HBV coinfection stop taking it.

Descovy was approved for PrEP in 2019 for some adults and adolescents at risk for sexually acquired HIV, including cisgender men and transgender women. However, due to a lack of evidence from trials, it is not yet indicated for people exposed to HIV through vaginal sex, such as cisgender women and trans men. TAF/FTC should be taken once daily, not on demand before and after sex.

The DISCOVER trial showed that daily TAF/FTC PrEP is as effective as daily TDF/FTC for cisgender men and transgender women.

TAF/FTC is generally safe and well tolerated, though it, too, can cause minor, usually temporary side effects. TAF is easier on the kidneys and bones than TDF, but it has been linked to elevated blood fat levels and possible weight gain. These drugs are also active against HBV. There is no generic equivalent for Descovy, so the cost is higher than generic TDF/FTC. (Click here to learn more about the differences between TDF and TAF.)

Apretude was approved for HIV prevention in 2021. It is indicated for all adults and adolescents at risk for sexually acquired HIV. It is given as an injection, usually in the buttocks, administered by a health provider for two consecutive months and then every other month. Another option is to start with cabotegravir pills (Vocabria) to assess tolerability.

The HPTN 083 trial showed that Apretude is even more effective than daily TDF/FTC for cisgender gay and bisexual men and transgender women. The HPTN 084 trial found that Apretude was substantially more effective than TDF/FTC for cisgender women in Africa, largely thanks to better adherence.

Apretude is generally safe and well tolerated, with no major adverse effects. The most common side effect is mild to moderate pain, redness or swelling at the injection site, which usually goes away after a few days.

Yeztugo was approved for HIV prevention in June 2025. It is indicated for all adults and adolescents at risk for sexually acquired HIV. PrEP starts with an initiation dose of lenacapavir pills for the first two days along with two injections, usually in the abdomen, administered by a health care provider. After that, two injections are given together every six months.

The PURPOSE 1 trial showed that twice-yearly lenacapavir was 100% effective for young cisgender women in Africa. The injections reduced HIV incidence compared with the background rate and were superior to daily TDF/FTC pills. The PURPOSE 2 study showed that the twice-yearly injections reduced the risk of HIV acquisition by 96% relative to background incidence and by 89% compared to TDF/FTC pills for gay and bisexual men and gender-diverse people.

Yeztugo is generally safe and well tolerated, with no major adverse effects. The most common treatment-related side effect is temporary injection site reactions. The long-acting injections form a “depot” under the skin that slowly releases the drug, which can sometimes be felt as a nodule.

How to Use PrEP 

PrEP is indicated for people who are at increased risk for sexually acquired HIV. This includes those who have condomless anal or vaginal sex with an HIV-positive person who does not have sustained viral suppression or whose status is unknown. In addition to PrEP, they should be offered risk-reduction counseling, adherence counseling and condoms. PrEP may also reduce the risk of acquiring HIV via shared drug injection equipment, but this has not been well studied.

According to the Centers for Disease Control and Prevention (CDC), providers should inform all sexually active adults and adolescents about PrEP and prescribe it to anyone who asks for it, as this may “help patients overcome embarrassment or stigma that could prevent them from telling their health care provider about their HIV risk factors.”

PrEP is indicated only for people who are HIV negative. It is important to get tested before starting PrEP, using an assay that can detect early infection, and at least every three months thereafter. People starting TDF/FTC or TAF/FTC should have their kidney function checked at the outset and monitored periodically. It is also important to get tested for hepatitis B before starting oral PrEP. Finally, people should be tested for sexually transmitted infections before starting PrEP and every three to six months thereafter.

Click here for the CDC’s PrEP guidance, IAS-USA’s PrEP recommendations (updated in 2024) and its new recommendation for Yeztugo.

Access to PrEP 

More than a decade after the FDA’s approval of Truvada for HIV prevention, PrEP has yet to reach its full potential. According to the CDC, less than a third of the 1.2 million people in the United States who could benefit from PrEP were using it in 2021. While many urban white gay men have eagerly adopted PrEP, uptake has been slower for other groups, including Black and Latino gay and bisexual men, women of all races and ethnicities, adolescents and young adults and people living in rural areas and the South.

 

Brand-name Truvada, Descovy, Apretude and Yeztugo are expensive, but most people can get PrEP for free or at reduced cost. Generic versions of TDF/FTC are now available at cost of around $30 a month.

The U.S. Preventive Services Task Force recommends PrEP for people at risk for sexually acquired HIV. This means insurers are required to fully cover PrEP at no cost. Medicare and Medicaid also cover PrEP, but state programs may vary in which options they include and coverage of associated services such as lab tests. In addition, Gilead Sciences (which makes Truvada, Descovy and Yeztugo) and ViiV Healthcare (which makes Apretude) offer financial assistance, and some cities and states have PrEP assistance programs. Your local AIDS service organization may have navigators or financial counselors who can help you access PrEP.

Last Reviewed: July 7, 2025